The treatment of tumors by Boron Neutron Capture Therapy (BNCT) requires the development of nontoxic boron compounds which will attain a differential boron concentration between tumor and normal tissues of at least 5 to 10:1. Such compounds should show persistence for a sufficient period of time that would ultimately allow for the delivery of a fractionated radiation dose to the tumor permitting repair from low linear energy transfer (LET) radiation in contiguous normal tissue. Ideally, the compounds should be localized in the cell nucleus since the radiobiological effectiveness is at least twice as great as it would be if the compounds were confined to the cytoplasm. The overall objective of this proposal is to synthesize and biologically evaluate boron-containing nucleic acid precursors such as carboranyl nucleotides and oligonucleotides that may possess a strong proclivity for malignant cells. The specific aims are: 1. To develop the methodology to synthesize carboranyl nucleosides and nucleotides with the boron moiety on the carbohydrate portion of the molecule. 2. To synthesize carboranyl nucleosides and cyclic nucleotides of adenine, guanine cytosine, thymine and other purine/pyrimidine bases. 3. Masking of the phosphate moiety of nucleotides to enhance cellular uptake and concentration by tumors. 4. To undertake the incorporation of carboranyl nucleotides into oligonucleotides as potential chemoradiotherapeutic agents. 5. To develop the methodology for radiolabeling these nucleic acid precursors. 6. To determine the in vitro cellular uptake and persistence of these boron-containing nucleosides and nucleotides in melanoma and glioma cells. 7. To study the in vivo pharmacokinetics and tumor-localizing properties of these compounds in tumor-bearing rats and mice. 8. To assess the tumorcidal activity both in vitro and in vivo of carboranyl nucleic acid precursors following thermal neutron irradiation.